Endocrinology III Flashcards
Where does Insulin act?
Muscle and fat
GLUT4 transporters
T/F
Insulin inhibits lipolysis
True
What becomes dominant when insulin decreases?
Glucagon - liver
Epinepherine - muscle
Why can’t insulin be given orally?
Peptide hormone
Type I diabetes is due to insulin _______.
Type II diabetes is due to insulin _______.
Deficiency
Resistance
What 3 requirements are there for a random plasma glucose Diabetes diagnosis?
Glucose > 200 mg/dl
polyuria
polydipsia
(and/or weight loss)
Why is there still high blood glucose in a diabetic in the fasting state?
There’s not enough insulin to get glucose from GNG and glycogenolysis into the cell.
Hemoglobin A1c glucose level above _____ suggests diabetes.
6.5%
T/F
Pre-diabetes always progresses to diabetes.
False
Define:
polyuria
polydipsia
polyphagia
(excessive)
urination
thirst
food intake
What contributes to diabetic hyperglycemia in the intestine and the kidney?
Intestine: decreases GLP-1
Kidney: SGLT-2 (glc transporter) over-expressed
What are some tests to confirm Type I diabetes?
GAD (glutamic acid decarboxylase antibody)
ICA (islet cell cytoplasmic autoantibodies)
*GAD long-lasting
There are many environmental factors leading to Type II diabetes. What are the 2 most important?
Obesity
Aging
What most often breaks in type II Diabetes?
Post-receptor actions
pre-receptor is rare and receptor defects not often
Ketones suggest…
Type I
What is a non-insulin treatment for Type II diabetes that decreases liver glc production and fasting glc?
Biguanide
metformin
What is an effective therapy for diabetes that stimulates beta cells, inhibits alpha cells, and decreases appetite?
Incretins
GLP-1
*expensive and effective
What do SGL2T2 inhibitors do?
inhibit excretion of glc
*newest drugs
What are the 2 background insulins?
long lasting, no peak
Glargine and Detemir
What does it mean if blood glucose is high before a meal in a diabetic?
The previous meal wasn’t covered enough by insulin
What can too much insulin cause?
Hypoglycemia
loss of consciousness
death
What are 2 hormonal causes of hypoglycemia?
GH or Cortisol deficiency
*these cause insulin resistance. With no insulin resistance, glucose is taken up by muscle and fat and not enough for the brain
What is a better treatment than snickers for hypoglycemia?
Glucagon injection
What leads to lipolysis in type I diabetes?
unopposed Glucagon
*ketoacidosis
What enzyme, suppressed by insulin, is over-active in response to epinephrine in type I diabetics?
Hormone Sensitive Lipase
*fat pours out of adipose tissue=ketoacidosis
Why does ketoacidosis not occur in Type 2 diabetes?
insulin deficient but not completely absent
What does high blood glucose, high urine glucose, and salt/water loss lead to?
Dehydration and High Serum Osmolality
What happens to tissues freely permeable to glucose in long-term diabetes?
They break down
Microangiopathies (retinopathy, neuropathy, nephropathy)
Macroangiopathy (cerebral, coronary, peripheral)
What are AGE’s?
Advanced Glycation Endproducts
*highly reactive consequence of too much glc
free radicals , cross linked proteins, etc.
What is ischemia?
Low oxygen to tissues
consequence of chronic hyperglycemia
What reduces inflammation in treatment for diabetic retinopathy?
Glucocorticoid
What risk factor goes way up in diabetic nephropathy?
heart disease
mortality 20-40 times higher
What is the mechanism of the slowed neural conduction in diabetic neuropathy?
semental demyelination
*distal first - which is why problems with feet
What are the conditions that comprise metabolic syndrome?
need 3 of these
Hyperinsulinemia Hyperglycemia Hypertriglyceridemia Low HDL cholesterol Hypertension Central obesity
What causes foot problems in diabetics?
Loss of feeling
Poor blood supply
Poor wound healing
(combined microvascular neuropathy and macrovascular disease)
Does intensive treatment of type I diabetes slow the onset of progression of disease?
Yes
*bigtime
Does intensive glucose control prevent macrovascular complications in Type II diabetes?
No.
*macrovascular disease outcomes the same
What two factors, if controlled, can benefit type II diabetes?
Blood pressure and Lipid control
How often should the feet be examined with a Diabetic patient?
What common drug can be useful in preventing other complications?
Daily
Aspirin
What do Leydig cells do?
Produce testosterone in presence of LH
*in testes
What is the function of Sertoli cells?
secrete mullerian inhibiting substance
“nurse” spermatogenisis process
When do gonads differentiate?
6 weeks
Describe the differentiation process at about 7 weeks.
Testosterone stimulates Wolffian ducts
Mullerian inhibiting substance degenerates Female (mullerian) ducts
What do the formation of the penis, scrotum, and prostate require?
What enzyme is involved?
DHT - dihydrotestosterone
5-alpha-reductase
*undervirillization usually defect in process (usually amount of DHT)
review:
Male gonad feedback loops
GnRH > LH/FSH > Testosterone
What stimulates the testes to make testosterone before and after 12 weeks?
Before 12 weeks: HCG (human chorionic gonadotropin) from placenta
After 12 weeks: FSH/LH from fetal pituitary
What does micropenis suggest?
Fetal pituitary failure
- low LH = low testosterone = low DHT = micropenis
- *must screen for other pituitary deficiencies
Testosterone effects the development of the ______ genitalia and dihydrotestosterone effects the development of the _____ genitalia.
Internal (vas defrens, etc)
External (scrotum, prostate, etc)
What does the maintenance of testicular germinal structures depend on?
Local testosterone
intra-testicular
What hormone stimulates the testes to produce testosterone?
LH
How are GnRH and LH/FSH secreted?
pulses
What type of cells are stimulated by LH?
FSH?
(in men)
LH - Leydig cells (testosterone)
(this diffuses to Sertoli cells)
FSH - Sertoli cells (Inhibin B)
*androgen binding protein
GnRH >
complete feedback
LH > Leydig cells > Testosterone
FSH > Sertoli cells > Inhibin
What can convert testosterone to estradiol?
Aromatase
found mostly in fat
What is the abnormal migration of GnRH-producing neurons and (bundled with) olfactory neurons called?
Kallman syndrome
*hypogonadism and no sense of smell
How are tertiary (hypothalamic) defects in sex hormones treated?
At primary level with testosterone
if fertility is the issue requires FSH/LH or GnRH via pump
HCG act in place of…
LH
If there is trouble at the testes what are hormone levels?
high GnRH, FSH, LH
low Testosterone
If someone is born without testes, what is the external genitalia?
female (internal and external)
When do testes fail in Klinefelter Syndrome?
After puberty
What are some target tissue defects in sexual differentiation?
Defective androgen receptor, 5-alpha-reductase (no DHT), aromatase (no estrogen)
If the testes are present but there are defective androgen receptors what would the hormone levels be?
high GnRH, FSH/LH, Testosterone, DHT, Estrogen
Why would androgen insensitivity syndrome produce no internal male or female genitalia?
Testosterone has no effect to produce male genitalia
Mullerian inhibiting hormone gets rid of internal female genitalia
Androgens refer to what 2 molecules?
Testosterone and DHT
What are the hormone levels in 5-alpha-reductase deficiency?
Normal everything.
*internal genitalia male, external female until puberty
What causes gynecomastia (excess breast tissue in males)?
excess Estrogen
(E/T ration high)
*common in aging
What condition includes the following: tall, epiphyses not closed, osteoporosis, normal genitalia, and abnormal semen?
No aromatase (so no estrogen) No estrogen receptors
Why would a continuous GnRH treatment be appropriate for prostate cancer?
GnRH that NOT in pulses down-regulates FSH and LH receptors
also, 5-alpha reductase inhibitors (no DHT) is a treatment for prostate cancer
What developmental indicators are affected by hormones?
height
length at birth, bone growth
Is brain size (head circumference) affected by hormones?
NO
*genetics, nutrition, environment
What 3 hormones affect length before birth?
insulin
IGF-1
IGF-2
T/F
Endocrine causes of childhood obesity is common
False
0.1%
T/F
Height after birth isn’t affected by hormones
FALSE
*GH and IGF-1
Describe the growth feedback loop
GHRH > GH > IGF-1
What does thyroid hormone do developmentally?
Height (acts in concert with GH)
Full fetal/child brain development
What are the 4 main hormones for growth?
GH
IGF-1
Thyroid hormone
Estrogen/testosterone (added at puberty)
*remember - estrogen closes epiphyses
What are some endocrine causes of short stature?
hypothyroidism
abnormal GH secretion
excess Cortisol
Precocious puberty
Thyroid hormone and GH both affect ____ more than _____.
height
weight
What effect does GH deficiency have on teeth?
gaps
small mandible
What does GH excess cause?
Gigantism or acromegaly
What is the difference between central and peripheral precocious puberty?
early puberty brought on by increases GnRH in Central
brought on by abnormal hormone source in Peripheral
How is central precocious puberty treated?
peripheral?
continuous GnRH
treat underlying cause
T/F
Hypothyroidism and GH deficiency can present similarly.
True
*fatigue, no growth in height, slow pulse, delayed deep tendon relaxation
